The primary objective of this investigation is the development of various NMR techniques including double resonance methods for delineating the detailed solution conformation of biomolecules in general, and two cell-differentiating pentapeptides and their analogs in particular. These pentapeptides are TP5 (Arg-Lys-Asp-Val-Tyr) and UB5 (Tyr-Asn-Ile-Gln-Lys). TP5 is a fragment of the thymic hormone thymopoietin, which induces differentiation of T-Lymphocytes, whereas, UB5 is a fragment of the immunopoietic polypeptide ubiquitin, which induces both T- and B-lymphocyte differentiation. Both TP5 and UB5 retain the differentiation inducing activity of their parent proteins. Comparison of the conformations of TP5 and UB5 with the conformations of their corresponding analogs (agonist and antagonists) will serve as a basis for the ultimate determination of the conformation-activity relationship of these peptides. An inherent advantage of the NMR techniques to be developed in this study is that they involve studies of the native biomolecule and do not require the introduction of an extrinsic probe, which may alter the conformation and/or the biological activity. A theoretical formalism is presented for quantitative interpretation of solvent saturation experiments in terms of parameters directly related to the extent of exposure to solvent of specific NH and CH protons. This formalism is based in part on the theory of intermolecular nuclear Overhauser effects of coupled spin systems previously derived by the principal investigator and his colleague Sidney Gordon. The "selective excitation" technique of Freeman will be adapted to studies of biomolecules in general and the two cell-differentiating peptides in particular. In addition to these methods to be developed in this study, the molecular structure and dynamics of these peptides will be investigated by more conventional methods involving vicinal spin-spin coupling constants, 13C spin-lattice relaxation times and paramagnetic shift and relaxation probes.